Researchers from Mass General Brigham and Albert Einstein College of Medicine identified molecular changes associated with type 2 diabetes risk, reflecting contributions from genetics, diet, and lifestyle factors, which could pave the way for more effective prevention and intervention strategies
BRONX, N.Y. and BOSTON, Jan. 14, 2026 /PRNewswire/ -- Diabetes, a metabolic disease, is on the rise worldwide, and over 90 percent of cases are type 2 diabetes, where the body does not effectively respond to insulin. Researchers from Mass General Brigham and Albert Einstein College of Medicine identified metabolites (small molecules found in blood generated through metabolism) associated with risk of developing type 2 diabetes in the future and revealed genetic and lifestyle factors that may influence these metabolites. They also developed a metabolomic signature that predicts future risk of type 2 diabetes beyond traditional risk factors. Their results are published in Nature Medicine.
In this study, researchers tracked 23,634 individuals with diverse ethnic backgrounds across 10 prospective cohorts with up to 26 years of follow-up. These individuals were initially free of type 2 diabetes. The team analyzed 469 metabolites in blood samples, as well as genetic, diet, and lifestyle data, to see how they relate to risk of developing type 2 diabetes. Of the metabolites examined, 235 were found to be associated with a higher or lower risk of developing type 2 diabetes, 67 of which were new discoveries.
"Interestingly, we found that diet and lifestyle factors may have a stronger influence on metabolites linked to type 2 diabetes than on metabolites not associated with the disease," said first and co-coresponding author Jun Li, MD, PhD, an assistant professor of Medicine and associate epidemiologist in the Mass General Brigham Department of Medicine. Li is also an assistant professor in the Department of Nutrition at Harvard T.H. Chan School of Public Health. "This is especially true for obesity, physical activity, and intake of certain foods and beverages such as red meat, vegetables, sugary drinks, and coffee or tea. Increasing evidence suggests that these dietary and lifestyle factors are associated with greater or lower risk of type 2 diabetes. Our study revealed that specific metabolites may act as potential mediators, linking these factors with type 2 diabetes risk."
The metabolites associated with type 2 diabetes were also found to be genetically linked to clinical traits and tissue types that are relevant to the disease. Furthermore, the team developed a unique signature of 44 metabolites that improved prediction of future risk of type 2 diabetes.
"Our study is the largest and most comprehensive investigation of blood metabolic profiles associated with the risk of type 2 diabetes that integrates genomic and diet and lifestyle data from a wide range of people, and lays important groundwork for future studies," said senior and co-corresponding author Qibin Qi, PhD, professor in the Department of Epidemiology & Population Health and associate director of that department's Center for Population Cohorts at Albert Einstein College of Medicine. "While these new findings offer important insights, additional experimental studies and clinical trials are needed to confirm the causality of these associations and clarify how these metabolic pathways contribute to the development of type 2 diabetes."
The collaborative research team plans to continue investigating why people develop diabetes through different biological pathways, with the goal of helping develop more targeted prevention strategies for individuals at high risk.
"A better understanding of the biological pathways behind disease can help drive the development of new treatments," said Li. "Our findings lay the groundwork for a deeper understanding of type 2 diabetes and may help inform the development of precision preventive strategies targeting specific metabolic pathways."
Authorship: In addition to Li, Mass General Brigham authors include Jie Hu, Zhendong Mei, Shilpa N. Bhupathiraju, A. Heather Eliassen, JoAnn E. Manson, Jose C. Florez, Miguel Angel Martínez-González, Kathryn M. Rexrode, James B. Meigs, and Frank B. Hu. In addition to Qi, Einstein authors include Kai Luo, Chengyong Jia, and Robert C. Kaplan. Additional authors include Huan Yun, Xingyan Wang, Marta Guasch-Ferré, Xikun Han, Buu Truong, Jordi Merino, Miguel Ruiz-Canela, Casey M. Rebholz, Eun Hye Moon, Taryn Alkis, Guning Liu, Jie Yao, Xiyuan Zhang, Bianca C. Porneala, Jordi Salas-Salvadó, Thomas J. Wang, Josée Dupuis, Elizabeth Selvin, Xiuqing Guo, Jennifer A. Brody, Yongmei Liu, Alexis C. Wood, Kari E. North, Su Yon Jung, Ching-Ti Liu, Nona Sotoodehnia, Simin Liu, Lesley F. Tinker, Robert E. Gerszten, Clary B. Clish, Liming Liang, Rozenn N. Lemaitre, Katherine L. Tucker, Stephen S. Rich, Jerome I. Rotter, Eric Boerwinkle, and Bing Yu.
Disclosures: Rich is a consultant to Westat, the Administrative Coordinating Center for the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. The remaining authors declare no competing interests.
Funding: The current study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) including R01DK119268 and R00DK122128. Other funding sources for this study include R01HL060712, R01HL170904, R01HL136266, and HHSN268201600034I (contract to the Broad Institute) from the National Heart, Lung and Blood Institute (NHLBI); R01DK126698, R01DK081572, U01DK140761, R01DK134672, R01DK120870, and the New York Regional Center for Diabetes Translation Research (P30DK111022) from NIDDK; R01AG085320 from National Institute on Aging; and a cooperative agreement UM1HG008898 from the National Human Genome Research Institute (NHGRI).
Paper cited: Li J et al. "Circulating metabolites, genetics, and lifestyle factors in relation to future risk of Type 2 diabetes" Nature Medicine DOI: 10.1038/s41591-025-04105-8
About Mass General Brigham
Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation's leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.
About Albert Einstein College of Medicine
Albert Einstein College of Medicine is one of the nation's premier centers for research, medical education and clinical investigation. Einstein is home to nearly 1,000 M.D., Ph.D., M.D./Ph.D. students, more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates, and six NIH-funded research centers in cancer, intellectual development disorders, clinical and translational research, AIDS, and two in diabetes. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. For more information, please visit einsteinmed.edu, follow us on Twitter, Facebook, Instagram, LinkedIn, and view us on YouTube.
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